Feline Leukemia Virus
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Feline leukemia virus (FeLV) is a
retrovirus A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase e ...
that infects
cat The cat (''Felis catus''), also referred to as the domestic cat or house cat, is a small domesticated carnivorous mammal. It is the only domesticated species of the family Felidae. Advances in archaeology and genetics have shown that the ...
s. FeLV can be transmitted from infected cats when the transfer of saliva or nasal secretions is involved. If not defeated by the animal's
immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
, the virus weakens the cat's immune system, which can lead to diseases which can be lethal. Because FeLV is cat-to-cat contagious, FeLV+ cats should only live with other FeLV+ cats. FeLV is categorized into four subgroups, A, B, C and T. An infected cat has a combination of FeLV-A and one or more of the other subgroups. Symptoms, prognosis and treatment are all affected by subgroup. FeLV+ cats often have a shorter lifespan, but can still live "normal", healthy lives.


Signs and symptoms

The signs and symptoms of infection with feline
leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...
virus are quite varied and include
loss of appetite Anorexia is a medical term for a loss of appetite. While the term outside of the scientific literature is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while o ...
, poor coat condition, anisocoria (uneven pupils), infections of the skin, bladder, and respiratory tract, oral disease,
seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...
,
lymphadenopathy Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In c ...
(swollen lymph nodes), skin lesions,
fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...
,
fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
,
weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...
, stomatitis, gingivitis, litter box avoidance,
pancytopenia Pancytopenia is a medical condition in which there is significant reduction in the number of almost all blood cells (red blood cells, white blood cells, platelets, monocytes, lymphocytes, etc.). If only two parameters from the complete blood cou ...
, recurring bacterial and viral illnesses,
anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
,
diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...
and
jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
. Asymptomatic carriers are still immune suppressed, with potential delayed and decreased antibody responses.


Progression

The disease has a wide range of effects. The cat can fight off the infection and become totally immune, can become a healthy carrier that never gets sick itself but can infect other cats, or a mid-level case in which the cat has a compromised immune system. Nevertheless, the development of lymphomas is considered the final stage of the disease. Although it is thought that virus protein has to be present to induce lymphomas in cats, newer evidence shows that a high percentage of FeLV-Antigen negative lymphomas contain FeLV-DNA, indicating a "hit-and-run" mechanism of virus-induced tumor development. Once the virus has entered the cat, there are six stages to a FeLV infection: # Stage One: The virus enters the cat, usually through the pharynx where it infects the epithelial cells and infects the tonsilar B-lymphocytes and macrophages. These white blood cells then filter down to the lymph nodes and begin to replicate. # Stage Two: The virus enters the blood stream and begins to distribute throughout the body. # Stage Three: The lymphoid system (which produces antibodies to attack infected and cancerous cells) becomes infected, with further distribution throughout the body. # Stage Four: The main point in the infection, where the virus can take over the body's immune system and cause viremia. During this stage the hemolymphatic system and intestines become infected. If the cat's immune system does not fight off the virus, then it progresses to: # Stage Five: The
bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
becomes infected. At this point, the virus will stay with the cat for the rest of its life. In this phase, the virus replicates and is released four to seven days later in infected
neutrophils Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in different ...
, and sometimes lymphocytes,
monocytes Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also i ...
, and
eosinophils Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along wi ...
(all white blood cells formed in the bone marrow). # Stage Six: The cat's body is overwhelmed by infection and mucosal and glandular epithelial cells (tissue that forms a thin protective layer on exposed bodily surfaces and forms the lining of internal cavities, ducts, and organs) become infected. The virus replicates in epithelial tissues including salivary glands, oropharynx, stomach, esophagus, intestines, trachea, nasopharynx, renal tubules, bladder, pancreas, alveolar ducts, and sebaceous ducts from the muzzle.


Transmission

Cat The cat (''Felis catus''), also referred to as the domestic cat or house cat, is a small domesticated carnivorous mammal. It is the only domesticated species of the family Felidae. Advances in archaeology and genetics have shown that the ...
s infected with FeLV can serve as sources of infection of FeLV-A. Cats can pass the virus between themselves through saliva and close contact, by biting another cat, and (rarely) through a litter box or food dish used by an infected cat. Once a cat has been infected with FeLV-A, additional mutated forms of the original FeLV-A virus may arise, as may FeLV subgroups B, C and T. In addition to domestic cats, some other members of
Felidae Felidae ( ) is the Family (biology), family of mammals in the Order (biology), order Carnivora colloquially referred to as cats. A member of this family is also called a felid ( ). The 41 extant taxon, extant Felidae species exhibit the gre ...
are now threatened by FeLV (e.g.
lynx A lynx ( ; : lynx or lynxes) is any of the four wikt:extant, extant species (the Canada lynx, Iberian lynx, Eurasian lynx and the bobcat) within the medium-sized wild Felidae, cat genus ''Lynx''. The name originated in Middle Engl ...
and
Florida panther The Florida panther is a North American cougar (''P. c. couguar'') population in South Florida. It lives in pinelands, tropical hardwood hammocks and mixed freshwater swamp forests. Its range includes the Big Cypress National Preserve, Everglade ...
). Overwhelming epidemiologic evidence suggests FeLV is not transmissible to either humans or dogs. Approximately 0.5% of pet cats are persistently infected with FeLV, but many more pet cats (>35%) have specific IgG antibodies which indicate prior exposure and subsequent development of
immunity Immunity may refer to: Medicine * Immunity (medical), resistance of an organism to infection or disease * ''Immunity'' (journal), a scientific journal published by Cell Press Biology * Immune system Engineering * Radiofrequence immunity ...
instead of
infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
. FeLV is highly infectious. Kittens can be born with it, having contracted it from their mother while ''in utero''. Infection is far higher in city cats, stray or owned, than in rural cats: this is entirely due to the amount of contact the cats have with each other.


Diagnosis and prognosis

Testing for FeLV is possible with
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...
tests that look for viral
antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
s, free particles found in the bloodstream. These ELISA tests use blood samples most often, but can also use saliva or eye secretions. The sample is added to a container or dish that contains the antibodies to the viral antigens. If the antigens are present in the sample, the antibodies will bind to them and an indicator on the test will change color. These give a definitive diagnosis, but it cannot differentiate between acute or persistent infections. Therefore, it is recommended that the cat be retested in three to four months after the positive result to determine if the virus has been cleared from the body. Diagnosis can also be made by reference lab testing, using an
immunofluorescence Immunofluorescence (IF) is a light microscopy-based technique that allows detection and localization of a wide variety of target biomolecules within a cell or tissue at a quantitative level. The technique utilizes the binding specificity of anti ...
(IFA) test. The IFA test uses a blood sample and will detect the virus once it is in the bone marrow by detecting the virus's presence in white blood cells. IFA testing will not give positive results for transient, primary infections – the infection must be persistent to get a positive result on this test. Other than ELISA and IFA testing, routine laboratory blood work may show changes that indicate infection but cannot be used as a definitive diagnosis. There may be blood cell count changes like
leukopenia Leukopenia () is a decrease in the number of white blood cells (leukocytes). It places individuals at increased risk of infection as white blood cells are the body's primary defense against infections. Signs and symptoms Symptoms may include: * s ...
, decreased Packed Cell Volume (PCV) and Total Protein (TP) levels due to
anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
, hemoconcentration and hypoglycemia due to vomiting and diarrhea, electrolyte imbalance caused by dehydration and anorexia, and recurrent urinary tract infections.Johnson, A. (2014). Small Animal Pathology for Veterinarian Technicians. Hoboken: Wiley Blackwell. Cats diagnosed as persistently infected by
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...
testing may die within a few months or may remain asymptomatic for longer; median survival time after diagnosis is 2.5 years. FeLV is categorized into four subgroups. # FeLV-A is responsible for the
immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...
characteristic of the disease. The vast majority of cats with FeLV have FeLV-A. An exception was reported in 2013. # FeLV-B causes an additional increase in the incidence of tumors and other abnormal tissue growths. About half of FeLV infected cats have FeLV-B. It forms by recombination of FeLV-A and cat endogenous FeLV (enFeLV). # FeLV-C causes severe anemia. Approximately 1% of FeLV infected cats have FeLV-C. It forms by mutation of FeLV-A. # FeLV-T leads to lymphoid depletion and immunodeficiency. It forms by mutation of FeLV-A. The fatal diseases are
leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...
s,
lymphomas Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...
, and non-regenerative
anemias Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
. Although there is no known cure for the virus infection, in 2006 the United States Department of Agriculture approved Lymphocyte T-Cell Immunomodulator as a treatment aid for FeLV (see Treatment). In Canada, one feline infected with progressive Feline Leukemia Virus Type C and its Immune-Mediated Hemolytic Anemia complication has been successfully managed so far for over 6 months with the use of high-dose corticosteroids, broad-spectrum antibiotics to treat opportunistic and comorbid infections, antiviral medications, and immunomodulators such as cyclosporine after requiring multiple packed red blood cell transfusions to raise a critically low blood cell count.


Prevention

Three types of vaccines for FeLV are available: an
adjuvant In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to: * Adjuvant therapy in cancer management * Anal ...
ed killed virus noninfectious vaccine, an adjuvanted subunit vaccine, and a nonadjuvanted canarypox virus-vectored recombinant infectious vaccine (
ATCvet The Anatomical Therapeutic Chemical (ATC) Classification System is a drug classification system that classifies the active ingredients of drugs according to the organ or system on which they act and their therapeutic, pharmacological and chemica ...
code QI066AA01 and various combination vaccines), though no currently available vaccine offers 100% protection from the virus. Vaccination is recommended for high-risk cats: those that have access to the outdoors, feral cats, cats that do not have the virus but live with an infected cat, multicat households, and cats with an unknown status, such as cats in catteries and shelters. Serious side effects have also been reported as a result of FeLV vaccination; in particular, a small percentage of cats who received the adjuvanted killed virus vaccine developed vaccine-associated sarcomas, an aggressive tumour, at the injection site. The development of sarcomas with the use of the old FeLV and other vaccines may be due to the inflammation caused by
aluminium Aluminium (or aluminum in North American English) is a chemical element; it has chemical symbol, symbol Al and atomic number 13. It has a density lower than that of other common metals, about one-third that of steel. Aluminium has ...
adjuvants in the vaccines.
Merial Boehringer Ingelheim Animal Health is a Multinational corporation, multinational animal health company, formed in January 2017 when Merial was acquired by Boehringer Ingelheim and merged with Boehringer Ingelheim's existing animal health assets. ...
produces a recombinant vaccine consisting of canarypox virus carrying FeLV ''gag'' and ''env'' genes (sold as PUREVAX FeLV in the US and Eurifel FeLV in Europe). This is thought to be safer than the old vaccine as it does not require an adjuvant to be effective. Although this is a live virus, it originates from a bird host and so does not replicate in mammals.


Viral structure

Feline leukemia virus (FeLV) is an RNA virus in the ''
Retroviridae A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase ...
'' family. The
virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...
comprises 5' and 3' LTRs and three genes: Gag (structural), Pol (enzymes) and Env (envelope and transmembrane); the total
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
is about 9,600
base pairs A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
.


Treatment


Approved US treatment

In 2006, the
United States Department of Agriculture The United States Department of Agriculture (USDA) is an executive department of the United States federal government that aims to meet the needs of commercial farming and livestock food production, promotes agricultural trade and producti ...
issued a conditional license for a new treatment aid termed Lymphocyte T-Cell Immunomodulator (LTCI). Lymphocyte T-Cell Immunomodulator is manufactured and distributed exclusively by T-Cyte Therapeutics, Inc. Lymphocyte T-Cell Immunomodulator is intended as an aid in the treatment of cats infected with feline leukemia virus (FeLV) and/or feline immunodeficiency virus (FIV), and the associated symptoms of
lymphocytopenia Lymphocytopenia is the condition of having an abnormally low level of lymphocytes in the blood. Lymphocytes are a white blood cell with important functions in the immune system. It is also called lymphopenia. The opposite is lymphocytosis, which r ...
,
opportunistic infection An opportunistic infection is an infection that occurs most commonly in individuals with an immunodeficiency disorder and acts more severe on those with a weakened immune system. These types of infections are considered serious and can be caused b ...
,
anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
,
granulocytopenia Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear, that is ...
, or
thrombocytopenia In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coag ...
. The absence of any observed adverse events in several animal species suggests that the product has a very low toxicity profile. Lymphocyte T-Cell Immunomodulator is a potent regulator of CD-4
lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), an ...
production and function. It has been shown to increase lymphocyte numbers and
Interleukin 2 Interleukin-2 (IL-2) is an interleukin, which is a type of cytokine signaling molecule forming part of the immune system. It is a 15.5–16 Dalton (unit), kDa protein that regulates the activities of white blood cells (leukocytes, often ...
production in animals. Lymphocyte T-Cell Immunomodulator is a single chain
polypeptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ...
. It is a strongly cationic
glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
, and is purified with cation exchange resin. Purification of protein from bovine-derived
stromal cell Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mu ...
supernatants produces a substantially homogeneous factor, free of extraneous materials. The bovine protein is homologous with other mammalian species and is a homogeneous 50 kDa glycoprotein with an isoelectric point of 6.5. The protein is prepared in a lyophilized 1 microgram dose. Reconstitution in sterile diluent produces a solution for subcutaneous injection.


Approved European treatment

Interferon-ω (omega) is sold in Europe at least under the name Virbagen Omega and manufactured by Virbac. When used in treatment of cats infected with FeLV in non-terminal clinical stages (over the age of 9 weeks) there have been substantial improvements in mortality rates; in non-anemic cats, mortality rate of 50% was reduced by approximately 20% following treatment.


History

FeLV was first described in cats in 1964. The disease was originally associated with leukemia; however, it was later realized that the initial signs are generally
anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
and
immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...
. The first diagnostic test became available in 1973, which led to a "test and elimination" regime, dramatically reducing the number of infected cats in the general population. The first vaccine became available in 1986.


Comparison with feline immunodeficiency virus

FeLV and feline immunodeficiency virus (FIV) are sometimes mistaken for one another, though the viruses differ in many ways. Although they are both in the same retroviral subfamily (Orthoretrovirinae), they are classified in different genera (FeLV is a gamma-retrovirus and FIV is a lentivirus like HIV-1). Their shapes are quite different: FeLV is more circular while FIV is elongated. The two viruses are also quite different genetically, and their protein coats differ in size and composition. Although many of the diseases caused by FeLV and FIV are similar, the specific ways in which they are caused also differ. Also, while the feline leukemia virus may cause symptomatic illness in an infected cat, an FIV infected cat can remain completely asymptomatic its entire lifetime.


See also

* Feline foamy virus (FFV) * Feline vaccination


References

* B. Zharkoy, A. Zolototrubov, D. Fedosov. "Intensity of free radical processes in limphocytes at BLV and FeLV". ''Journal of Animal Science''. XLII,5/2005, p. 272–276.


External links


Lymphocyte T-Cell Immunomodulator (LTCI)

Feline Leukemia Virus (FeLV) from Veterinary Partner

Feline leukemia Treatments and Support

Feline Leukemia Virus from Cornell Feline Health Center

Feline Leukemia Virus Infection (FeLV) in Cats


{{Authority control Cat diseases Gammaretroviruses Animal viral diseases Vaccine-preventable diseases